tbuckley/cabot-search huggingface dataset:
Clinical value of timely targeted therapy (TT) for patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADO).
Authors: Thomas Stricker, Neha Jain, Elaine Yu, Esprit Ma, Robert Schuldt, Rongrong Wang, Jesse Sussell, Sarika Ogale, Tania Szado, Richard Price, Victor T. G. Lin, Dennis Slater, Daniel A. Vaena, Harry Staszewski, Bruno Fang, Lasika Seneviratne, Edward Arrowsmith, Davey B. Daniel
Journal: Journal of Clinical Oncology (2023)

6507 Background: Recent real-world studies observed that some aNSCLC pts with ADO initiated non-targeted therapy (non-TT) before biomarker test results became available. This study assesses the clinical impact of the timing of first line (1L) TT in aNSCLC pts with ADO. Methods: In a retrospective analysis of the nationwide Flatiron Health electronic health record-derived de-identified database, pts aged ≥18 years, diagnosed (Dx) with aNSCLC between 1/1/2015-10/18/2022, had ADO (ALK, BRAF, EGFR, RET, MET, ROS-1, or NTRK) based on biomarker testing ≤ 90 days of advanced Dx, and received 1L treatment (tx) were included. Cohorts were defined by tx patterns after test result: Cohort 1 received 1L TT ≤ 42 days; Cohort 2 initiated 1L non-TT before or after testing but switched to TT ≤ 42 days; Cohort 3 initiated non-TT before or after testing and did not switch to TT ≤ 42 days. Pts were followed from test results + 42 days until 11/30/2022 or death, whichever earliest. Multivariate Cox regression evaluated real-world progression-free survival (rwPFS) and overall survival (OS) between cohorts. Results: A total of 5156 aNSCLC pts with ADO were included: 79% were treated in the community setting and 56% received NGS testing. Most common ADO were EGFR and ALK for both Cohort 1 (78% and 13%) and Cohort 2 (67% and 24%); EGFR (39%) and BRAF (35%) for Cohort 3. Cohort 3 included more rare mutations (MET, NTRK, RET). Statistically significant differences were observed in gender, race/ethnicity, practice type, and area-level socioeconomic status across all cohorts. There was no significant difference in outcomes observed between Cohort 2 and 1, but significantly inferior outcomes in Cohort 3 vs 1. Conclusions: Our findings demonstrated better outcomes with upfront 1L TT vs non-TT in aNSCLC pts with ADO. The comparable outcomes between pts who received 1L TT after test result and pts who switched to TT ≤ 42 days of test result available underscore the importance of timely tx decisions based on ADO detection in lieu of tx-switch at progression. Opportunities remain to improve utilization of NGS to identify all ADO upfront to inform the appropriate 1L TT when indicated. [Table: see text]
What differences in outcomes exist in Hispanic patients being treated for lymphoplasmacytic lymphoma and waldenstrom macroglobulinemia?
Authors: Jacob Huston-Cravens, Maria Elena Fierro, Qianqian Liu, Joel Michalek, Adolfo Enrique Diaz Duque
Journal: Journal of Clinical Oncology (2023)

e19541 Background: Lymphoplasmacytic Lymphoma (LPL) and Waldenstrom Macroglobulinemia (WM) are both rare diseases with little known about their longterm outcomes in ethnic minorities. Overall, the 5- and 10-year survival of this disease has improved over the last 60 years (Blood, PMID: 24948623), but few studies have explored outcomes in Hispanic (HI) patients. We analyzed demographics, treatment patterns and outcomes in patients diagnosed with LPL and WM comparing HI and Non-Hispanics (NH) in the US. Methods: Data was analyzed on LPL and WM patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) analyzing patient characteristics, age-adjusted incidence rate, and survival rate among HI and NH patients. Results: HI were diagnosed at a younger median age on both LPL and WM cohorts compared to NH (p &lt;0.001). There was a higher percentage of HI patients diagnosed with LPL and WM before the age of 60 compared to that of NH (p &lt;0.001). Regarding race of patients with LPL, most of both HI and NH patients identified as whites (94% vs 86%), followed by blacks (2% vs 6%). Regarding stage, a majority of both HI (50%) and NH (60%) patients diagnosed with LPL were Stage IV. In terms of radiation, 7% of HI patients with LPL received it, compared to 4% of NH patients (p=0.027). On survival analysis for LPL patients, the survival probability at 2, 5 and 10 years (y) of HI vs NH were similar. There was not an OS difference favoring HI/NH (p=0.49). On survival analysis for WM patients, the survival probability at 2, 5 and 10 y of HI vs NH were similar. The median survival time for patients with WM was similar between HI and NH patients and there was not OS difference favoring HI vs NH (p=0.16). On multivariate analysis for LPL and WM, those diagnosed over the age of 80 had worse OS compared to those younger than 60 (95% CI; 4.8-8.1 and 2-3.4, respectively). No OS benefit when adjusting for stage was observed for either LPL or WM. Conclusions: In LPL and WM patients HI patients were diagnosed at younger ages compared to NH for both LPL and WM, and more likely to be diagnosed before the age of 60. The median survival rates were similar between HI and NH patients diagnosed with both LPL and WM. These findings may be confounded by earlier diagnosis in HI patients; however, further studies are needed exploring biological ethnic differences to explain early diagnosis in LPL and WM among HI.
Integration analysis of single-cell multi-omics in the prostate cancer ecosystem.
Authors: Xiaojie Bian, Wenfeng Wang, Mierxiati Abudurexiti, Zhu Yao, Min Zhang, Ding-Wei Ye, Jianhua Wang
Journal: Journal of Clinical Oncology (2023)

e17046 Background: Prostate cancer (PCa) is characterized as a extensive heterogeneous disease with the complex cellular ecosystem in the tumor microenvironment (TME). However, the content of how heterogeneity is shaped by tumors and stromal cells or vice versa remains poorly understood. Methods: Single-cell RNA sequencing, spatial transcriptomics and bulk ATAC-sequence from a series of human PCa and normal control were integrated. Results: We identified a stemness subset of club cells marked with SOX9 high AR low expression, which enriched significantly after neoadjuvant androgen-deprivation therapy (ADT). Furthermore, a subset of CD8 + CXCR6 + T cell, functioned as effector T cell, was observed to be markedly reduced in the malignant PCa patients. Notably, immunosuppressive microenvironment in advanced PCa was associated with infiltration of regulatory T cells (Tregs), which is potentially induced by FAP + fibroblasts (cancer-associated fibroblasts, CAFs subset). Moreover, for spatial transcriptome analysis, we comprehensively utilized machine learning and computational intelligence to identify cellular diversity of prostate and cell-cell communication with each other in situ.Importantly, we also depicted macrophage and neutrophil state transition under different biological conditions in vivo. Conclusions: We delineate the cellular heterogeneity in the stage-specific PCa microenvironment at single-cell resolution, uncover their reciprocal crosstalk with disease progression and these results will be helpful in exploring potential target for PCa therapy.
Phase 1b study of batiraxcept (AVB-S6-500, BT) plus gemcitabine (G) and nab-paclitaxel (NP) as first-line treatment (1L) for advanced pancreatic adenocarcinoma (PDAC).
Authors: Vaibhav Sahai, Paul Eliezer Oberstein, Smitha S. Krishnamurthi, Nashat Y. Gabrail, Christos Fountzilas, Warren S. Brenner, Zev A. Wainberg, Hongxia Yan, Gail McIntyre, Charles D. Lopez, Niharika B. Mettu, Robert B. Geller
Journal: Journal of Clinical Oncology (2023)

e16258 Background: PDAC is a deadly aggressive cancer characterized by up to 80% tumor stroma enriched by macrophages, fibroblasts, and collagen deposition that influences resistance to therapy. Tyrosine kinase receptor AXL and ligand expression of growth arrest specific protein 6 (GAS6) produce tumor associated macrophages and fibroblasts and correlate with poor prognosis. GAS6 blockade partially reverses epithelial-to-mesenchymal transition of tumor and supports NK cell activation, inhibiting metastasis. As a novel decoy FC fusion protein, batiraxcept (BT) binds to GAS6 and demonstrates highly potent and specific AXL inhibition. Preclinical studies showed a relationship between AXL signaling and response to DNA damage in PDAC models. Methods: This dose escalation study tested BT 15 mg/kg on day 1 and 15 in combination with G 1000 mg/m 2 and NP 125 mg/m 2 days 1, 8, 15 of a 28-day cycle. Primary endpoints are safety and objective response rate (ORR) using RECIST v1.1; key secondary endpoints are progression free survival (PFS) and overall survival (OS); pharmacokinetic data were collected to determine exposure-PFS response (E-R) relationship. Results: As of January 17, 2023, 21 patients (pts) received BT/G/NP of which 10 (48%) were male and 3 (14%) received prior neoadjuvant/adjuvant therapy. BT-related AEs &gt; 10% pts included fatigue (n=7, 33%), diarrhea (n=4, 19%), infusion related reaction and neutropenia (n=3, 14% each). Grade ≥ 3 BT-related AE occurred in 6 pts (29%). BT administration reduced GAS6 to non-quantifiable levels until treatment ended. 18 pts (86%) discontinued treatment, primarily due to toxicity (n=2) and progressive disease (n=13). Median (m) BT/G/NP treatment duration was 13.1 weeks (range 0.1─74.7). ORR is 29%; mPFS and mOS were 5.4 mo (2.1, 5.6) and 12.3 mo (4.11─NE) respectively. BT efficacy results are described by a minimally efficacious concentration (MEC) of 14.5 mg/L identified by E-R modeling. Conclusions: BT/G/NP combination was well tolerated, and the BT safety profile is consistent with prior trials. Patients with BT trough &gt; MEC had longer PFS and OS. In addition, in these patients OS appears longer than historical data of 8.5 months. Due to increased stroma seen in PDAC, a higher BT MEC may be required to maximize efficacy. Higher BT dose levels in combination with G/NP are under study. Clinical trial information: NCT04983407 . [Table: see text]
A prediction model for response to immune checkpoint inhibition in advanced melanoma.
Authors: Isabella A.J. van Duin, Rik Jasper Verheijden, Paul J. van Diest, Alfonsus Johannes Maria van den Eertwegh, Jan Willem de Groot, Olivier Jules van Not, Maureen J.B. Aarts, Franchette Van Den Berkmortel, Christian U. Blank, John B. A. G. Haanen, Geke Hospers, Djura Piersma, Rozemarijn van Rijn, Astrid Aplonia Maria Van Der Veldt, Gerard Vreugdenhil, Marion Stevense - den Boer, Marye J. Boers-Sonderen, Ellen Kapiteijn, Karijn Suijkerbuijk, Sjoerd G. Elias
Journal: Journal of Clinical Oncology (2023)

9532 Background: Immune checkpoint inhibition (ICI) has greatly improved the prognosis for advanced melanoma in the last decade. However, it is still difficult to predict who will benefit from treatment. We aimed to develop a multivariable prediction model for response to ICI, using clinical data including primary melanoma characteristics. Methods: We used a population-based cohort of 3525 patients with advanced cutaneous melanoma treated with anti-PD-1-based therapy, originating from the Dutch Melanoma Treatment Registry. The endpoint of the study was objective response to ICI within 6 months after treatment initiation. The model considered 15 candidate predictor variables, was developed with logistic regression using Akaike information criterion-informed backward selection, and was internally validated with bootstrap resampling. Performance evaluation included calibration and discrimination. We used multiple imputation to account for missing data. Results: Patients received anti-PD-1 monotherapy (n = 2366) or ipilimumab plus nivolumab (n = 1159) in any treatment line. Median follow-up time was 15 months and 1311 patients (39%) had an objective response within 6 months. The prediction model for response included sex, serum lactate dehydrogenase, World Health Organization performance score, type of systemic therapy, line of systemic therapy, stage of disease, location of primary melanoma, type of primary melanoma, satellites and/or in transit metastases at time of primary diagnosis, and time to first distant recurrence. The model was well-calibrated. The AUC was 0.664 (95% confidence interval [CI] 0.645-0.682), and the over-optimism adjusted AUC was 0.649 (95% CI 0.631-0.667). The range of predicted response probabilities was 6-78%. Based on these probabilities, patients were categorized into quartiles. The median predicted response probability was 25% (interquartile range [IQR] 21-28%) for the lowest quartile and 54% (IQR 50-59%) for the highest quartile. Compared to the lowest response quartile, patients in the highest quartile had a significant longer median PFS (19.9 versus 2.8 months; p &lt; 0.001) and median OS (66.5 versus 8.4 months; p &lt; 0.001). Conclusions: We present a model based on both clinical variables and primary melanoma characteristics capable of predicting response to ICI in patients with advanced melanoma. This model can discriminate between patients with a very good and very poor prognosis.
Survival outcomes of sarcomatoid versus classic urothelial carcinoma of bladder.
Authors: Rohan Garje, Ahmad Ozair, Meenakkshy Manoharan, Pushan Prabhakar, Muni B. Rubens, Mukesh Roy, Anshul Saxena, Atulya Aman Khosla, Bruno R. Bastos, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2023)

4588 Background: Sarcomatoid urothelial carcinoma (SUC), a rare bladder cancer variant, has both epithelial and mesenchymal differentiation along with frequent TERT C228T promoter mutations and has poorer prognosis. In this study, we compared survival outcomes of SUC with classic urothelial carcinoma (CUC) in patients with T2-T4, N0-N1 bladder cancer after definitive therapy. Methods: All cases meeting our inclusion criteria for SUC and CUC during 2004-2019 were identified from National Cancer Database. Sociodemographic and clinicopathological characteristics were analyzed via descriptive and comparative statistics. Propensity-score matching was performed to adjust for baseline differences between SUC and CUC. Overall survival (OS) was compared using Cox proportional-hazards modelling and visualized through Kaplan-Meier curves. Results: 30072 cases of CUC and 480 of SUC were identified. Propensity-score matching resulted in N = 478 patients in both groups. Matched cohorts had no baseline differences in age, sex, race, comorbidities, insurance status, income, distance to hospital, hospital location, rural versus urban residence, histological grade, and proportion getting regional lymph node surgery. Overall, there were 675 males and 281 females, 435 underwent surgery (Sx), and 521 surgery plus chemotherapy (Sx+Cx). For SUC, median survival with Sx vs Sx+Cx was 29.5 months (95%CI 20.0-50.6) vs 43.1 months (95%CI 25.3-64.4) respectively. For CUC, median survival was 56.1 (95%CI 53.7-58.6) vs 78.0 (95%CI 75.1-81.1) months with Sx vs Sx+Cx respectively. Conclusions: SUC has poorer prognosis than CUC. Perioperative chemotherapy along with surgery was associated with improved survival outcomes compared to surgery alone in patients with SUC. Further studies investigating novel immunotherapy agents are warranted to improve oncologic outcomes. [Table: see text]
Impact of COVID-19 pandemic on the treatment of prostate cancer in the Brazilian public health system.
Authors: Gustavo Carvalhal, Igor Alexandre Protzner Morbeck, Daniel Herchenhorn, Andre Deeke Sasse, Rana R. McKay, Brent Shane Rose, Fernando Cotait Maluf, Fernando Sabino Marques Monteiro, Vinicius Carrera, Andrey Soares, Denis L. Jardim, Diogo Assed Bastos, Elcio Firminiano, Douglas Andreas Valverde, Nick James
Journal: Journal of Clinical Oncology (2023)

e17106 Background: COVID-19 pandemic reached Brazil in the beginning of 2020 causing a profound impact in economic and social activities, up to the end of 2021. In Brazil, there is universal access to the public health system (BPHS-SUS); however, during the pandemic public resources were directed mainly to the management of COVID-19 infected patients. We evaluated the impact of the 2020/2021 pandemic on the treatment of prostate cancer in the BPHS-SUS. Methods: we compared data regarding the number of radical prostatectomies, radiotherapy treatments, and hormonal and chemotherapy treatments administered in the time frame from March 1 st , 2020 (when lockdown measures were initially adopted in Brazil) to February 29 th , 2022, with that of the two most recent pre-pandemic years (March 1 st , 2018, to February 28 th , 2020). A large proprietary healthcare data science platform offered by TECHTRIALSÒ was surveyed. Results: in the two pandemic years, 15,196 radical prostatectomies were performed in the BPHS, with a cost of U$ 14,271,297; there was a 23.3% reduction in the number of surgeries compared with the two pre-pandemic years (19,818 radical prostatectomies, with a cost of U$ 18,056,470). In the pandemic, 34,982 men were treated with radiation therapy, with a cost of U$ 39,616,736; this meant a 18.7% reduction in the number of patients treated with radiation therapy as compared with the two pre-pandemic years (43,013 men, with a cost of U$ 44,148,190). Regarding hormonal treatments, numbers were similar: 116,490 men were treated during the pandemic (cost of U$ 74,834,615); in the pre-pandemic timeframe, 115,949 patients received hormonal therapy (cost of U$ 75,179,674). As to chemotherapy for hormone-resistant disease, in the pandemic 14,946 men were treated (cost of U$ 23,402,947) compared with 12,695 men treated in the two pre-pandemic years (cost of U$ 19,239,099). Conclusions: there was a significant reduction in the number of radical prostatectomies and of radiation therapy treatments during the pandemic years in the BPHS-SUS. Abrupt reductions of potentially curative therapies will probably affect stage migration, costs to the public system and patients’ survival in the ensuing years. The number of systemic therapies (first- and second-line hormonal therapies, and chemotherapies) were slightly increased, probably reflecting the BPHS-SUS policy of maintaining systemic treatments active during the pandemic.
Cryptococcosis in non-HIV/non-transplant hematological patients: A 12-year retrospective clinical analysis in a Peruvian referral cancer center.
Authors: Kelly Meza, Alexis Holguin, Juan Velarde, Claudio Intimayta-Escalante, Oliver Sulca-Huamani, Ebert Poquioma, Jose Ernesto Vidal, Luis E Cuellar
Journal: Journal of Clinical Oncology (2023)

e19536 Background: Globally, cryptococcal infection has become a public health challenge. However, relatively little is known about cryptococcal infection in non-HIV/non-transplant oncohematological patients. Methods: We developed a retrospective cohort study that includes hematological patients who had cryptococcosis infection seen in the Instituto Nacional de Enfermedades Neoplasicas between 2007 and 2018. We exclude HIV and transplant recipients patients. Results: During the 12-year study period, among 14908 individuals with hematological malignancies (HM), a total of 21 cases of cryptococcosis were identified, representing an incidence rate of 1.41 per 1000 HM diagnosed in our center. Non-Hodgkin lymphoma (NHL) (47.6%), acute leukemias (23.8%), multiple myeloma (19.1%), and Hodgkin lymphoma (9.5%). Three cases of adult T-cell leukemia/lymphoma were identified. The sub-group analysis showed that NHL (7.35 per 1000 NHL) and Multiple myeloma (4.59 per 1000 MM) had the highest incidence rates. Regarding the clinical presentation, the time between the diagnosis of cryptococcosis and HM was 42 (18–161) days. Cryptococcal fungemia and antigenemia was the most frequent diagnosis (85.7%), followed by pulmonary (52.4%) and central nervous system (38.1%) involvement. At the time of the diagnosis of cryptococcosis, 61.5% were receiving chemotherapy, 53.9% were in the induction phase, and 7.7% were on maintenance therapy. The use of immunosuppressants and chemotherapy within a month of the diagnosis of cryptococcosis was the most common risk factor (90.5%). Regarding the subanalysis performed between the different types of malignancies (NHL versus other HM), age at admission (p = 0.02), site of cryptococcosis presentation (p = 0.01), and lymphocyte count at admission (p = 0.01) were statistically different between these groups. In the NHL subgroup, there was less involvement of the lungs and higher fungemia (p = 0.01). The overall survival (OS) of our cohort at 15 and 120 days was 70% (95%CI: 0.43-0.86) and 51% (95%CI: 0.26-0.72), respectively. OS for patients with NHL was 57% at 15 days (95% CI: 0.17-0.83) and 42% at 120 days (95%CI:0.09-0.73). OS for other HM was 90% at 15 days (95%CI:0.47-0.98) and 60% at 120 days (95%CI: 0.25-0.82). Conclusions: Our cohort characterized the distinct clinical presentation, risk factors, and outcomes of cryptococcal infection in hematologic malignancies subgroups. NHL was the HM with the worst prognosis and the highest incidence rate. [Table: see text]
Evaluating triple therapy with lenvatinib, PD-1 inhibitor and transarterial chemoembolization for unresectable intrahepatic cholangiocarcinoma: A retrospective study.
Authors: Jianfei Tu, Xihui Ying, Lingqiang Lai, Chaoming Huang, Shuang Liu, Li Chen, Dengke Zhang, Jiahao Wu, Jie Chen
Journal: Journal of Clinical Oncology (2023)

e16210 Background: Cholangiocarcinoma has a poor prognosis and responds poorly to intravenous chemotherapy. This study evaluated the efficacy and safety of a triple therapy combining transarterial chemoembolization (TACE) with lenvatinib and programmed cell death protein (PD)-1 inhibitors for treating unresectable intrahepatic cholangiocarcinoma (ICCA). Methods: This retrospective study included a total of 15 patients with unresectable ICCA who were initially treated with TACE. One week later, they received lenvatinib 8 mg/day orally and PD-1 inhibitors for 21 days/cycle. The primary endpoint was the objective response rate (ORR); secondary endpoints included disease control rate (DCR), overall survival (OS), progression-free survival (PFS), and the incidence of treatment-related adverse events (TRAEs). Results: At 1-month post-treatment, the ORR was 73.3% and the DCR was 86.7%. The median PFS was 10.4 months (95% confidence interval [CI]: 6.73, not reached), and the median OS was 16.9 months (95% CI: 9.2, not reached). Compared with pre-treatment data, post-treatment levels of the tumor serum markers carcinoembryonic antigen and carbohydrate antigen 19-9 had decreased significantly (P&lt;0.05). However, 13 patients experienced Grade 1–2 TRAEs, including decreased appetite (n=8 [53.3%]), fatigue (n=3 [20.0%]), weight-loss (n=3 [20.0%]), hypertension (n=2 [13.3%]), hand–foot syndrome (n=2 [13.3%]), diarrhea (n=1 [6.7%]), dysphonia (n=1 [6.7%]), and hypothyroidism (n=1 [6.7%]). No patient experienced Grade ≥3 TRAEs during treatment or follow-up. Conclusions: Triple therapy with TACE, lenvatinib and PD-1 inhibitors showed promising antitumor activity as well as a tolerable safety profile in patients with ICCA. Larger clinical studies investigating this treatment combination should be considered.